Approximately 127 million (65%) Americans are overweight, obese, or morbidly obese, and the number of obese Americans is rising. Obesity negatively affects general health and has been attributed to an increasing incidence of diabetes, heart disease, vascular disease, joint stress, lumbar spine disorders, liver and biliary disease, and various cancers. Currently, there are no image-guided or percutaneous interventions or alternatives to the current invasive surgical techniques for the morbidly obese. Moreover, these surgical approaches have variable success rates, are highly invasive (requiring reconstruction of bowel), and can have significant complications. Thus, a critical need exists for minimally invasive bariatric procedures to reduce the perioperative complication rate and cost of bariatric therapy. A potent endogenous hunger stimulant, ghrelin, which is principally produced in the gastric fundus, has been a target for weight loss. No clinically viable, non-surgical approaches to modulate ghrelin production have been developed to-date. However, our group has manipulated ghrelin levels and altered weight gain via embolization of the arterial supply to the fundus of the stomach in pigs. Bariatric gastric Artery Embolization (BAE) is a complicated procedure as multiple vessels supply the stomach, and branches of these same vessels supply multiple other key structures, such as the spleen, pancreas, and liver. Thus, the risk of non-target embolization of these key structures as well as injury or ulceration to the gastric mucosa is a concern. Unlike embolic therapy for cancer which is primarily palliative, if successful BAE could allow patients to lose weight, lower risk factors for other diseases, and live long productiv lives. Thus, critical issues such as improved targeting, safety, and long term efficacy need to be further addressed in order to translate this procedure from the swine model into patients. In this proposal, we will improve BAE using advances in technology including specialized injection devices, X-ray visible embolic beads, and state-of-the-art X-ray imaging systems in order to produce a more complete fundal embolization with fewer adverse effects from non-target embolization and mucosal damage. Through this we hope to achieve prolonged ghrelin suppression and sustained weight loss. Our Specific Aims include: 1) Improved targeting of the gastric fundus using X-ray visible embolic beads of varying sizes, cone beam CT, and an anti-reflux embolic catheter; 2) Improved safety of BAE by assessing the effect of gastroprotective medications; and 3) determining the long term safety and efficacy of optimized BAE to both suppress ghrelin and alter weight.